RNA-Seq of regenerating DRG neurons
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE59547 | GEO | 2017/07/12
SECONDARY ACCESSION(S): PRJNA255530
REPOSITORIES: GEO
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Project description:Nerve injury in the peripheral nervous system allows spontaneous regeneration, in contrast to injury of central nerves, which lead to a differential expression pattern of regeneration-associated genes and others. These genes might be regulated by promoter DNA methylation As regeneration model, DRG tissue was analyzed for methyated gene promoters and CpG islands following both injury types. A differential methylation pattern could be identified, although most genes remained unmethylated. comparison of DRG following either sciatic nerve axotomy (SNA) or dorsal column axotomy (DCA) - each 'real injury or sham' - at 1, 3 or 7 days post-injury vs. 'naive', Each sample was pooled from two mice, yielding an immunoprecipitated sample ('Test') and an input genomic DNA sample (Ref). altogether 33 microarrays were used for 13 conditions with triplicate arrays for 'real injury' or 'naive' samples, and duplicate arrays for 'sham' samples.
2014-03-05 | E-GEOD-55514 | biostudies-arrayexpress
Project description:Purpose: compare the gene expression in whole DRG of mice: A) undergone to nerve axotomy vs control condition B) pre-exposed to EE and undergone to nerve axotomy vs control condition Results: we found that EE_SNA induces transcriptional changes strongly promoting axon regeneration. We call this "Enriched Conditioning"
2020-10-12 | GSE138769 | GEO
Project description:Axon regeneration is a necessary step toward functional recovery after spinal cord injury. The AP-1 transcription factor c-Jun has long been known to play an important role in directing the transcriptional response of Dorsal Root Ganglion (DRG) neurons to peripheral axotomy that results in successful axon regeneration. Here we performed ChIPseq for Jun in mouse DRG neurons after a sciatic nerve crush or sham surgery in order to measure the changes in Jun’s DNA binding in response to peripheral axotomy. We found that the majority of Jun’s injury-responsive changes in DNA binding occur at putative enhancer elements, rather than proximal to transcription start sites. We also used a series of single polypeptide chain tandem transcription factors to test the effects of different Jun-containing dimers on neurite outgrowth in cortical and hippocampal neurons. These experiments demonstrated that dimers composed of Jun and Atf3 promoted neurite outgrowth in rat CNS neurons. Our work provides new insight into the mechanisms underlying Jun’s role in axon regeneration.
2018-08-06 | GSE105442 | GEO
Project description:Successful regeneration of injured neurons requires a complex molecular response that involves the expression, modification and transport of large numbers of proteins. The neuronal proteins responsible for the initiation of regenerative neurite outgrowth are largely unknown. Dorsal root ganglion (DRG) neurons display robust and successful regeneration following lesion of their peripheral neurite, whereas outgrowth of central neurites is weak and does not lead to functional recovery. We have utilized this differential response to gain insight in the early transcriptional events associated with successful regeneration. Surprisingly, our study shows that peripheral and central nerve crushes elicit very distinct transcriptional activation, revealing a large set of novel genes that are differentially regulated within the first 24 hours after the lesion. A large number of known regeneration associated genes were retrieved in our study, and, in addition, hundreds of novel genes possibly involved in the transcriptional regulatory network underlying successful regeneration. Please refer to Stam et al., Eur. J. Neurosci 25:3629 (2007). Keywords: time course
2007-07-09 | GSE5762 | GEO
Project description:In contrast to CNS neurons, dorsal root ganglia (DRG) neurons can switch to a regenerative state after peripheral axotomy. In a screen for chromatin regulators of the regenerative responses in this conditioning lesion paradigm, we identified Tet methylcytosine dioxygenase 3 (Tet3) as upregulated, along with increased 5-hydroxymethylcytosine (5-hmC) in DRG neurons. We generated genome-wide 5-hmC maps in adult DRG, which demonstrated that peripheral and central axotomy (no regenerative effect) triggered differential 5-hmC changes that are associated with distinct signaling pathways. 5-hmC was altered in half of regeneration-associated genes (RAGs), supporting its role for RAG regulation. Our analyses predicted transcription factors HIF-1, STAT and IRF that may collaborate with Tet3 for 5-hmC modifications. Intriguingly, central axotomy lead to widespread 5-hmC modifications with little overlap with peripheral axotomy, thus potentially constituting a roadblock for regeneration. Our study revealed 5-hmC as a previously unrecognized epigenetic mechanism underlying the divergent responses after axonal injury.
2016-12-09 | GSE85972 | GEO
Project description:Functionally distinct subtypes/clusters of dorsal root ganglion (DRG) neurons may play different roles in nerve regeneration and pain. However, details about their transcriptomic changes under neuropathic pain conditions remain unclear. Chronic constriction injury (CCI) of the sciatic nerve represents a well-established model of neuropathic pain, and we conducted single-cell RNA-sequencing (scRNA-seq) to characterize subtype-specific perturbations of transcriptomes in lumbar DRG neurons on day 7 post-CCI. By using PirtEGFPf mice that selectively express an enhanced green fluorescent protein in DRG neurons, we established a highly efficient purification process to enrich neurons for scRNA-seq. We observed the emergence of four prominent CCI-induced clusters and a loss of marker genes in injured neurons. Importantly, a portion of injured neurons from several clusters were spared from injury-induced identity loss, suggesting subtype-specific transcriptomic changes in injured neurons. Moreover, uninjured neurons, which are necessary for mediating the evoked pain, also demonstrated cell-type-specific transcriptomic perturbations in these clusters, but not in others. Notably, male and female mice showed differential transcriptomic changes in multiple neuronal clusters after CCI, suggesting transcriptomic sexual dimorphism in DRG neurons after nerve injury. Using Fgf3 as a proof-of-principle, RNAscope study provided further evidence of increased Fgf3 in injured neurons after CCI, supporting scRNA-seq analysis, and calcium imaging study unraveled a functional role of Fgf3 in neuronal excitability. These findings may contribute to the identification of new target genes and the development of DRG neuron cell-type-specific therapies for optimizing neuropathic pain treatment and nerve regeneration.
2022-10-24 | GSE216039 | GEO
Project description:Preconditioning nerve injury drives pro-regenerative perineuronal macrophage activation in dorsal root ganglia (DRG). The present study reports that oncomodulin (ONCM) is produced from the regeneration-associated macrophages (RAMs) and strongly influences regeneration of DRG sensory axons. ONCM in macrophages was necessary to produce RAMs in the in vitro model of neuron-macrophage interaction and played an essential role in for preconditioning-induced neurite outgrowth. In order to gain insight on potential mechanisms downstream of ONCM for potent neurite outgrowth activity, we performed RNA-seq using cultured DRG neurons treated with ONCM.
2022-01-21 | GSE193893 | GEO
Project description:Chronic, often intractable pain is caused by neuropathic conditions such as peripheral nerve injury (PNI) and spinal cord injury (SCI). These conditions are associated with alterations in gene and protein expression correlated with functional changes in somatosensory neurons having cell bodies in dorsal root ganglia (DRGs). Most studies of DRG transcriptional alterations have utilized PNI models where axotomy-induced changes important for regeneration may overshadow changes that drive neuropathic pain. Both PNI and SCI produce DRG neuron hyperexcitability linked to pain, but contusive SCI produces little peripheral axotomy or peripheral nerve inflammation. Thus, comparison of transcriptional signatures of DRGs across PNI and SCI models may highlight pain-associated transcriptional alterations that don’t depend on peripheral axotomy and associated effects such as peripheral Wallerian degeneration. Data from our rat thoracic SCI experiments were combined with meta-analysis of whole-DRG RNA-seq datasets from prominent rat PNI models. Striking differences were found between transcriptional responses to PNI and SCI, especially in regeneration-associated genes and long noncoding RNAs. Many transcriptomic changes after SCI were also found after corresponding sham surgery, indicating they were caused by injury to surrounding tissue rather than to the spinal cord itself. Another unexpected finding was of few transcriptomic similarities between any rat neuropathic pain model and the only reported transcriptional analysis of human DRGs linked to neuropathic pain. These findings show that DRGs exhibit complex transcriptional responses to central and peripheral neural and tissue injury. Although few genes in DRG cells show similar changes in gene expression across all these painful conditions, the few widely shared transcriptional alterations promise novel insights into fundamental mechanisms within DRGs that can drive neuropathic pain.
2022-10-20 | GSE202111 | GEO
Project description:Dorsal root ganglion (DRG) neurons provide connectivity between peripheral tissues and spinal cord. Transcriptional plasticity within DRG sensory neurons after peripheral nerve injury contributes to nerve repair but also leads to maladaptive plasticity, including the development of neuropathic pain. This study presents tissue and neuron specific expression profiling of both known and novel Long Non-Coding RNAs (LncRNAs) in rodent DRG following nerve injury. We have identified a large number of novel LncRNAs expressed within rodent DRG, a minority of which were syntenically conserved between mouse and rat and which including both- intergenic and antisense LncRNAs. We have also identified neuron type-specific LncRNAs in mouse DRG, and LncRNAs that are expressed in human IPS cell-derived sensory neurons. We show significant plasticity in LncRNA expression following nerve injury, which in mouse is strain dependant. This resource is publicly available and will aid future studies of DRG neuron identity and the transcriptional landscape in both naïve and injured DRG.
2017-11-21 | GSE107180 | GEO
Project description:Primary sensory neurons with cell soma in dorsal root ganglia (DRG) project axons in both the peripheral nervous system and the spinal cord. Whereas the peripheral axon can regenerate after injury, the central axon cannot, providing an opportunity to identify the mechanisms that promote axon regeneration. Using this system, multiple intrinsic mechanisms operating in sensory neurons have been shown to promote axon regeneration. Peripheral sensory neurons also benefit from a supportive environment. In particular, macrophages play important roles in nerve regeneration by clearing debris and regulating Schwann cell function at the site of injury in the nerve. Nerve macrophages have been characterized at the molecular level and derive for the most part from infiltrating monocytes. However, the role and origin of macrophages in the DRG remains poorly understood. Following a 14-days treatment with a CSF1R inhibitor, less than 10% of macrophages remained in the DRG. Recovery from this treatment resulted in a dramatic macrophage repopulation, with the number of DRG macrophages reaching level similar to untreated mice three days post injury. These repopulated DRG macrophages contribute to promote axon regeneration. Our scRNA-seq analysis allow in-depth characterization of the repopulated DRG macrophages in response to nerve injury. These data will provide a better understanding of DRG macrophages and the molecular mechanisms by which they contribute to peripheral nerve repair. These studies may lead to new potential targets to promote axon regeneration.
2023-02-07 | GSE190283 | GEO